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The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.
Verbeure, W, Deloose, E, Tóth, J, Rehfeld, JF, Van Oudenhove, L, Depoortere, I, Tack, J
American journal of physiology. Endocrinology and metabolism. 2021;(1):E1-E10
Abstract
Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1) the site of administration: intragastrically (IG) or intraduodenally (ID), 2) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg), or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min before administration and every 10 min after administration for a period of 2 h. Hunger was rated at the same time points on a visual analogue scale. ID bitter administration did not affect hunger sensations, motilin, or acyl-ghrelin release compared with its placebo infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50 and 70 min after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 min before food intake.NEW & NOTEWORTHY Bitter tastants are a potential new weight-loss treatment. This is a noninvasive, easy approach, which should be received with considerable enthusiasm by the public. However, literature about bitter administration lacks consistency in methods and findings. We summarize how the compound should be given based on: the site of administration, the best bitter compound to use, and at what timing in respect to the meal. This paper is therefore a fundamental step to continue research toward the further development of the "bitter pill."
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2.
Gastric accommodation: Physiology, diagnostic modalities, clinical relevance, and therapies.
Febo-Rodriguez, L, Chumpitazi, BP, Sher, AC, Shulman, RJ
Neurogastroenterology and motility. 2021;(12):e14213
Abstract
BACKGROUND Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post-Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high-resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume. PURPOSE Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.
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3.
The effect of intestinal glucose load on neural regulation of food craving.
Stopyra, MA, Friederich, HC, Sailer, S, Pauen, S, Bendszus, M, Herzog, W, Simon, JJ
Nutritional neuroscience. 2021;(2):109-118
Abstract
Objectives: Excess sugar consumption, particularly in the form of sweetened beverages, has been identified as a pivotal contributor to the epidemic of obesity and associated metabolic disorders. However, the impact of sugar-sweetened beverages on food craving is still inconclusive. Therefore, the present study aimed to specifically investigate the effects of an intestinal glucose load on neural processing of food cues. Methods: Using a single-blind fMRI design, 26 normal-weight women were scanned on two occasions, after receiving either a glucose or water infusion directly into the stomach using a nasogastric tube, without being aware of the type of infusion. Participants had to either view neutral and food images, or were asked to distract themselves from these images by solving an arithmetic task. Results: In response to viewing high-caloric food cues, we observed increased activation in reward-related brain areas. During food distraction, fronto-parietal brain regions were recruited, which are commonly related to attentional deployment and hedonic valuation. Furthermore, activity in the dorsolateral prefrontal cortex showed increased functional connectivity with the insula and was correlated with subjective craving levels to food cues. Despite an increase of blood glucose levels in response to the glucose compared to the water infusion, neither subjective food craving nor neural regulation of food craving showed significant differences. Conclusions: These findings support a decreased satiation effect of sweet beverages, as intestinal glucose ingestion and signalling showed no significant effect on cortical brain circuits associated with food craving. This trial was registered at clinicaltrials.gov as NCT03075371.
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Gastric emptying of "clear liquid drinks" assessed with gastric ultrasonography: a blinded, randomized pilot study.
Pai, SL, Bojaxhi, E, Logvinov, II, Porter, S, Feinglass, NG, Robards, CB, Torp, KD
Minerva anestesiologica. 2020;(2):165-171
Abstract
BACKGROUND Protein-containing liquids may delay gastric emptying and increase risk of aspiration. Commercial whey protein nutritional drinks (WPNDs) are advertised as "clear liquid nutritional drinks" and can be mistaken for protein-free, carbohydrate-based clear liquids. We used gastric ultrasonography to compare gastric emptying of a protein-free, carbohydrate-based clear liquid with that of a WPND in healthy volunteers. METHODS We recruited 19 adult (age ≥18 years) volunteers with a body mass index less than 40 kg/m2 and without a history of diabetes mellitus, dysphagia, prior gastric surgery, or allergy to the ingredients of apple juice (AJ) or a WPND. After fasting for eight hours, the volunteers randomly received 474 mL of AJ or a WPND. Gastric ultrasonographic measurements were obtained at baseline and at 0, 30, 60, and 120 minutes after ingestion of the liquid. RESULTS We enrolled 19 volunteers. At 120 minutes after consumption, volunteers who ingested a WPND had a larger estimated gastric volume (GV) than volunteers who ingested AJ (median [interquartile range], 101.3 [70.0-137.4] vs. 50.6 [43.9-81.8] mL; P=.08). By using the 2-sample t test and an α level of .05, we determined that the study had 40% power to detect a significant difference in GV. Future studies need to include 24 participants per group to detect a significant difference. CONCLUSIONS Although consumption of a WPND was associated with a larger estimated GV in this pilot study, a larger study is necessary to conclude whether patients must fast longer than two hours after consumption of a WPND.
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Destructuring and restructuring of foods during gastric digestion.
Guo, Q, Ye, A, Singh, H, Rousseau, D
Comprehensive reviews in food science and food safety. 2020;(4):1658-1679
Abstract
All foods harbor unique length scale-dependent structural features that can influence the release, transport, and utilization of macro- or micronutrients in the human gastrointestinal tract. In this regard, food destructuring and restructuring processes during gastric passage significantly influence downstream nutrient assimilation and feelings of satiety. This review begins with a synopsis of the effects of oral processing on food structure. Then, stomach-centric factors that contribute to the efficacy of gastric digestion are discussed, and exemplified by comparing the intragastric de- and restructuring of a number of common foods. The mechanisms of how intragastric structuring influences gastric emptying and its relationship to human satiety are then discussed. Finally, recently developed, non-destructive instrumental approaches used to quantitively and qualitatively characterize food behavior during gastric destructuring and restructuring are described.
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6.
Application of the GastroDuo to study the interplay of drug release and gastric emptying in case of immediate release Aspirin formulations.
Schick, P, Sager, M, Voelker, M, Weitschies, W, Koziolek, M
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2020;:9-17
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Abstract
The process of gastric emptying is of major importance for the in vivo performance of immediate release dosage forms. In the fed state, this process consists of two phases: the rapid emptying of water along the "Magenstrasse" and the continuous emptying of the chyme. The relevance of these phases for the pharmacokinetic (PK) profile of a drug depends on the release behavior from its dosage form. It was the aim of this study to investigate the role of gastric emptying for the pharmacokinetics of a fast disintegrating and dissolving Aspirin® tablet (FDDT). For this purpose, a three way pharmacokinetic study with 30 healthy volunteers was performed to investigate the performance of the FDDT under fasted and fed conditions and compare it to a regular Aspirin® tablet (RT) administered in the fed state. Plasma samples were taken at predetermined time points and analyzed by LC MS/MS. In the second part of this work, both products were tested in a biorelevant dissolution test device - the GastroDuo. To simulate the occurrence of the Magenstrasse at different time points, two test programs have been applied. The results of the PK study clearly demonstrated the superiority of the FDDT over the RT. We observed an earlier tmax (0.39 h vs. 2.00 h) and a higher Cmax (6.33 ± 2.37 μg/mL vs. 3.23 ± 1.28 μg/mL), whereas the AUC was only slightly different between both formulations. The administration of the FDDT together with food had no marked effect on tmax (0.34 h vs. 0.39 h), but caused a decrease in Cmax compared to fasted intake (14.76 ± 4.81 μg/mL vs. 6.33 ± 2.37 μg/mL). This effect could be explained by the in vitro data collected with the GastroDuo. The FDDT showed a faster drug release and improved emptying kinetics in the GastroDuo. In contrast, the RT showed incomplete emptying in both test programs. Thus, the early tmax observed for the FDDT under fed conditions could be related to the presence of the Magenstrasse. In contrast, drug release from the RT was insufficient to allow gastric emptying via the Magenstrasse, which resulted in later tmax. This study highlighted the importance of gastric emptying for immediate release dosage forms and illustrated that the application of suitable formulation techniques provides a strategy to generate a fast and reliable onset of drug plasma concentrations even in the fed state.
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Percutaneous CT-Guided Cryovagotomy.
Prologo, JD
Techniques in vascular and interventional radiology. 2020;(1):100660
Abstract
There are a number of pathologic conditions in the human body that may be modified by the interruption of neural signaling, both related to pain and otherwise. Many of these treatments currently involve implantable neuromodulation or frank surgical neural ligation, representing opportunities for the implementation of percutaneous device-mediated cryoneurolysis in interventional radiology. Computed tomography-guided cryovagotomy for the management of mild to moderate obesity represents one such opportunity currently under investigation. This procedure is designed to attenuate hunger signals by targeting the posterior vagal trunk using computed tomography for cryoablation with a needle, based on historical surgical and electrical vagotomy experience. Future investigations of this technique and others will expand and iterate the concept of percutaneous, image-guided cryoneurolysis as potential management for a wide variety of clinical challenges.
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Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution.
Jalleh, R, Pham, H, Marathe, CS, Wu, T, Buttfield, MD, Hatzinikolas, S, Malbert, CH, Rigda, RS, Lange, K, Trahair, LG, et al
Nutrients. 2020;(7)
Abstract
Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = -0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.
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The influence of gastric motility on the intraluminal behavior of fosamprenavir.
Braeckmans, M, Brouwers, J, Masuy, I, Servais, C, Tack, J, Augustijns, P
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2020;:105117
Abstract
In fasting conditions, the gastrointestinal system contracts according to the interdigestive migrating motor complex (MMC), in which phases of quiescence (MMC phase I) alternate with phases of medium (MMC phase II) to very strong (MMC phase III) contractions. The time of drug intake relative to this cyclic motility pattern may cause variations in formulation behavior. To explore this hypothesis, a cross-over study was performed in healthy volunteers with an immediate release tablet of fosamprenavir (Telzir) which was administered in either MMC phase I or MMC phase II, as determined by high-resolution manometry. In the intestinal tract, fosamprenavir is rapidly hydrolyzed to the active compound amprenavir by alkaline phosphatases. Drug concentrations of both prodrug and drug were determined in the stomach and duodenum and linked to simultaneously assessed systemic concentrations. In 5 out of 6 healthy volunteers, the gastric release of fosamprenavir and the systemic uptake of amprenavir were affected by the MMC phase in which the tablet was administered. The intragastric disintegration of the tablet was faster and less variable after administration in MMC phase II, resulting in faster and less variable uptake of amprenavir in the systemic circulation. Mean plasma tmax values were 157 (±72.0) and 73.3 (±27.3) min after administration in MMC phase I and MMC phase II, respectively. The study clearly identified the time of oral drug intake relative to the interdigestive motility pattern as a possible source of variation in gastrointestinal drug behavior and absorption.
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Postoperative nutritional outcomes and quality of life-related complications of proximal versus total gastrectomy for upper-third early gastric cancer: a meta-analysis.
Lee, I, Oh, Y, Park, SH, Kwon, Y, Park, S
Scientific reports. 2020;(1):21460
Abstract
Although proximal gastrectomy (PG) provides superior nutritional outcomes over total gastrectomy (TG) in upper-third early gastric cancer (EGC), surgeons are reluctant to perform PG due to the high rate of postoperative reflux. This meta-analysis aimed to comprehensively compare operative outcomes, nutritional outcomes, and quality of life-related complications between TG and PG performed with esophagogastrostomy (EG), jejunal interposition, or double-tract reconstruction (DTR) to reduce reflux after PG. After searching PubMed, Embase, Medline, and Web of Science databases, 25 studies comparing PG with TG in upper-third EGC published up to October 2020 were identified. PG with DTR was similar to TG regarding operative outcomes. Patients who underwent PG with DTR had less weight reduction (weighted mean difference [WMD] 4.29; 95% confidence interval [0.51-8.07]), reduced hemoglobin loss (WMD 5.74; [2.56-8.93]), and reduced vitamin B12 supplementation requirement (odds ratio [OR] 0.06; [0.00-0.89]) compared to patients who underwent TG. PG with EG caused more reflux (OR 5.18; [2.03-13.24]) and anastomotic stenosis (OR 3.94; [2.40-6.46]) than TG. However, PG with DTR was similar to TG regarding quality of life-related complications including reflux, anastomotic stenosis, and leakage. Hence, PG with DTR can be recommended for patients with upper-third EGC considering its superior postoperative nutritional outcomes.